Age-related standards for T lymphocyte subsets based on uninfected children born to human immunodeficiency virus 1-infected women*

Giaquinto, Carlo; Zacchello, Franco; Rossi, Anita De; Bianchi, Luigi; Wörner, I.; Hauck, M.; Mok, Jacqueline; Bird, A. G.; Terés, Félix Omeñaca; Rodrı́guez, Marı́a C.; Zapico, R. Jmartinez; José, María Isabel de; Fontán, G; Ferreira, A.; Canosa, C. A.; Scherpbier, H. J.; Roos, M. T. L.; Bohlin, Ann Britt; Ferrazin, Antonio; Gotta, Cristina; Bassetti, Dante; Levy, Jack S.; Mur, Antonio; Yazbeck, H.; Llorens-Terol, J

doi:10.1097/00006454-199211120-00006

Cited by 110 publications

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“…Despite the presence of this CCR5 ϩ CD4 ϩ T cell subset in the gut, the majority of CD4 ϩ T cells in neonates exhibit a naive phenotype and are skewed functionally toward immune tolerance (14)(15)(16)(17)(18). In light of these phenotypic and functional differences, along with the higher CD4 ϩ T cell levels in children than in adults, the age-related declines of CD4 ϩ T cells in infants (19)(20)(21), an overall lower number of activated memory target cells in neonates than in adults, and no strong evidence indicating higher systemic CD4 ϩ T cell depletion in infants (22)(23)(24), it remains unclear what is driving the faster and more severe disease progression in pediatric cases. This highlights the importance of further defining T cell immune responses in HIV progression as well as the response of other immune cells that are targeted by infection such as macrophages.…”

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confidence: 99%

Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques

Sugimoto

Merino

Hasegawa

et al. 2017

J Virol

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Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4 T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU] CD163), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants. HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model, this work was performed to address why infants infected with SIV progress more quickly to AIDS than do adults. Earlier we reported that in adult rhesus macaques, increasing monocyte turnover reflected tissue macrophage damage by SIV and was predictive of terminal disease progression to AIDS. Here we report that uninfected infant rhesus macaques exhibited a higher physiological baseline monocyte turnover rate than adults. Furthermore, once infected with SIV, infants displayed further increased monocyte turnover that may have facilitated the accelerated progression to AIDS. These results support a role for monocytes and macrophages in the pathogenesis of SIV/HIV and begin to explain why infants are more prone to rapid disease progression.

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